Conformational and inframolecular studies of the protonation of adenophostin analogues lacking the adenine moiety

Four adenophostin analogues lacking the adenine moiety were subjected to 31P- and 1H-NMR titrations in order to determine the acid-base behaviour of the individual ionisable groups of the molecules and the complex interplay of intramolecular interactions resulting from the protonation process. For the two trisphosphorylated compounds, the curve pattern of the phosphorus nuclei corresponds to the superimposition of the titration curves of a monophosphorylated polyol and a polyol carrying two vicinal phosphates, suggesting that the two phosphate moieties behave independently. Also, the general shape of 1H-NMR titration curves of the studied compounds is very close to that of adenophostin A, indicating that the adenine moiety does not specifically interact with the phosphorylated sugar moieties. The curves show, however, that both trisphosphorylated compounds adopt slightly different preferential conformations which could contribute to explain the difference in their affinity for Ins(1,4,5)P3 receptor. Their macroscopic as well as the microscopic protonation constants are higher than those of adenophostin A, indicating that the adenine moiety plays a base-weakening effect on the phosphate groups. Further analysis of the microscopic protonation constants confirms that the compound whose conformation is the closest to that of adenophostin A also shows the highest biological activity. The two bisphosphorylated analogues studied behave very similarly, suggesting that the deletion of the hydroxymethyl group on the pentafuranosyl ring only weakly influences the protonation process of the phosphate groups that bear the glucopyranose moiety.     

Colloidal effect of albumin on the placental lactogen and chorionic gonadotrophin releases from human term placental explants

Albumin has been reported to stimulate the release of placental lactogen and chorionic gonadotrophin from human term placental explants within physiological concentrations. This study aimed at characterizing further its effect on the placental hormonal secretion. The placental lactogen and chorionic gonadotrophin secretory response of incubated explants to 5% albumin was reproduced by colloidal agents, i.e., dextran (4.5%) and polygelin (4%), indicating that a rise in colloidal osmotic pressure can elicit hormonal release from the syncytiotrophoblast. Their secretory effects were not modified by the absence of extracellular calcium or the presence of verapamil in the medium. The three agents also provoked a marked increase in (45)calcium outflow from preloaded and perifused explants that persisted in absence of extracellular calcium. These data indicate that the triggering effect of albumin on placental lactogen and chorionic gonadotrophin release can be partly reproduced by colloidal agents and is independent of extracellular calcium.     

Spatial sex segregation in the dioecious grass Poa ligularis in northern Patagonia: the role of environmental patchiness

We examined the effect of environmental patchiness on the spatial segregation of the sexes in the dioecious anemophilus grass Poa ligularis. Because the species is sensitive to grazing, a better understanding of environmental factors that control its spatial distribution and abundance could improve conservation efforts. We hypothesized that (i) males and females are spatially segregated in the microenvironments created by plant patches as the result of sexual specialization in habitat and/or resources use, (ii) sexual specialization is related to different tolerance to competition and reproductive costs of males and females, and (iii) changes in patch structure affect the microenvironment and the intensity of spatial segregation of the sexes. We analyzed the spatial distribution of sexes at three sites with different plant and micro-environmental patchiness and performed a controlled competition experiment with different substitution of males and females. Our results showed that large plant patches created larger sheltered soil fertility islands than small patches. As patch size and their area of influence increased, the density and the spatial segregation of the sexes of P. ligularis also increased, resulting in biased habitat-specific sex ratios. In accordance with their higher reproductive costs, females were more frequent in sheltered (low air evaporative demand) and nitrogen-rich areas inside patch perimeters than males. Females were also better able to tolerate inter-sexual competition than males. In contrast, males tolerated low nitrogen concentration in soil and low sheltering, probably gaining advantage in pollen dispersal. Inter- and intra-sexual competition, however, affected the reproductive output of both sexes. From the point of view of conservation, environmental patchiness is important to the status of P. ligularis populations. The reduction of patch size limits the available microsites, biases the sex ratio towards males inside patches, increases inter- and intra-sexual competition, and it might be expected to decrease overall seed and pollen production and consequently potential recruitment.     

Phosphate metabolism and foetal growth in the rat. II. Net transfer of 31P and 32P inorganic phosphate from the maternal plasma to the normal foetus

Net transfer of 31P and 32P inorganic phosphate from the maternal plasma to the rat foetus has been studied after intraperitoneal injection of [32P] ortho-phosphate in primigravid females at the 12th day or later stages of gestation. The concentration per unit weight of foetus of the inorganic phosphate (P1) fraction increases markedly with increasing foetal weight; labelling data [inverse relationship between P1 concentration and specific activity, absence of precursor/product relationship between P1 and acid-soluble organic-bound phosphates (POAS)] show this increase to result in part from the formation of a relatively inert metabolic pool, presumably in mineralized tissue. The foetal concentrations of calcium and inorganic phosphate show a strong positive correlation, both increasing markedly with foetal weight. The progressive accumulation of calcium does not, however, account entirely for the rising concentration of inorganic phosphate. The concentration per unit weight of foetus of the POAS fraction remains stable for foetuses smaller than 2 000 mg. In heavier foetuses (greater than 2 000 mg) the POAS concentrations are, with an abrupt transition, distinctly lower, rising however slightly with increasing foetal weight. The concentration per unit weight of foetus of the acid-insoluble organic-bound phosphate (POAIS) fraction decreases slightly with increasing foetal weight. The label uptake per unit weight of foetus of both POAS and POAIS fractions is negatively correlated with increasing foetal weight. The amount and label uptake per whole foetus of the P1, POAS and POAIS fractions are positively correlated with increasing foetal weight. Phosphate transfer to the foetus increases continuously, being maximal at or near birth.     

Fine mapping of the gene for autosomal dominant juvenile-onset glaucoma with iridogoniodysgenesis in 6p25-tel

Glaucoma is a group of ocular disorders leading to reduced visual capabilities and sometimes blindness. The biochemical defect is unknown but it is shown that reduced drainage of the aqueous humour from the anterior chamber may lead to increased intraocular pressure and gradual atrophy of the optic neurons. Families with various forms of autosomal dominant (AD) glaucoma have been linked to 1q21-31, 2cen-q13, 4q25-27, and 13q14 and autosomal recessive congenital glaucoma have been localized to chromosome 1p36 and 2p21. Recently, a locus for AD iridogoniodysgenesis anomaly (IGDA) was mapped to chromosome 6p25. This study refines the localization of IGDA to an approximately 6–cM interval between D6S1600 and D6S1617/D6S1713 at 6p25-tel, based on recombinations in affected individuals with AD juvenile-onset glaucoma and concomitant iridogoniodysgenesis. Received: 5 May 1997 / Accepted: 15 June 1997